Viral infections have a debilitating effect on the economic output of society. Diagnosis is commonly difficult, and the availability of treatments limited. As a result, an infected individual must routinely battle the virus as it runs its course. In some instances, this battle is never won, as viral infections can become persistent. Hepatitis C virus (HCV) infection becomes chronic in up to 85% of infected individuals1. This is a serious worldwide public health concern, constituting a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The mechanisms for the high rate of viral persistence are unknown, and as a result, progress in the development of vaccine and antiviral therapies has been impeded. Viruses with RNA genomes such as HCV, can undergo mutation at high frequencies, and under appropriate selective pressure, rapidly generate viral variants. Distinctive among RNA viruses infecting humans, HCV is the only virus (with the exception of retroviruses) that persists in the majority of infected individuals. The hypervariable region 1 (HVR1), located in a stretch of 27-31 residues at the amino terminus of the second envelope glycoprotein (E2) has been identified as a main target of the anti-HCV neutralizing response, and is involved in the establishment of viral persistence11,12. However, the role of HVR1 in viral persistence has come into question in light of a recent study demonstrating that infection with modified HCV genomic RNA, without HVR1, although attenuated in growth, can cause persistent infection in chimpanzees, thus suggesting that HVR1 is not essential for HCV progression to chronicity10.
Current commercial enzyme immunoassays (EIAs) for diagnosis of hepatitis C virus (HCV) infection, for example, have two major limitations: (i) their sensitivity is inadequate to detect seroconversion before 5-6 weeks post-infection leading to a prolonged window period (residual risk in blood supply is 1/100,000) (ii) their sensitivity is poor, causing an unacceptable false positive rate (40 to 50% in blood donors). Although nucleic acid testing will play an increasingly important role in narrowing the window period, it is technically complex and is not cost-effective.
The sensitivity of third generation EIAs for detection of anti-HCV antibodies has been improved by using a combination of viral proteins, as antigens, however, a prolonged window period to detection of seroconversion of HCV infection and a low specificity when testing the low risk populations such volunteer blood donors remains. Thus, improvements to current screening and detection methods for biological products is important for the safety of such products as well as for the cost-effectiveness of health care in general.
Although studies have investigated the diversity of persistent infection, a systematic characterization of viral persistence has not been previously developed. Accordingly, a need exists for a fundamental understanding of the mechanisms of viral infection and persistence as a basis to provide effective diagnosis and treatment regimes. Such an understanding would also provide a basis for the development of accurate and reliable detection systems for detecting viral infection.
Furthermore, current viral detection methods and/or systems are not capable of characterizing a viral infection, with respect to its capacity to persist in a host, for example. It would be beneficial to have indicators of viral behavior that are useful in characterizing a viral infection. The ability to characterize a viral infection would further serve to improve the determination of an effective treatment regime.
In this respect, there is a further need for the development of specific treatment regimes, tailored to target pre-characterized viral infections.